Peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (HCC) and other cancers

Abstract

A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), in which the peptide is in a complex with an MHC molecule.

The invention claimed is: 
     
       1. A method of eliciting a CD8+ cytotoxic T cell response in an HLA-A*02+ patient who has hepatocellular carcinoma (HCC), comprising
 identifying the patient who has HCC cells that over-present on the cell surface a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) as compared to a panel of normal tissues, wherein the peptide is in a complex with HLA-A*02, and 
 administering to said identified patient a composition comprising a population of activated antigen-specific CD8+ cytotoxic T cells to kill the HCC cells in the identified patient, 
 wherein the population of activated antigen-specific CD8+ cytotoxic T cells recognize the HCC cells by interacting through their TCR with a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) in a complex with HLA-A*02 presented at the surface of the HCC cells. 
 
     
     
       2. The method of  claim 1 , wherein the activated antigen-specific CD8+ cytotoxic T cells are autologous to the patient. 
     
     
       3. The method of  claim 1 , wherein the activated antigen-specific CD8+ cytotoxic T cells are obtained from a healthy donor. 
     
     
       4. The method of  claim 1 , wherein the activated antigen-specific CD8+ cytotoxic T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells. 
     
     
       5. The method of  claim 1 , wherein the composition further comprises an adjuvant. 
     
     
       6. The method of  claim 5 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23. 
     
     
       7. A method of eliciting a CD8+ cytotoxic T cell response in an HLA-A*02+ patient who has hepatocellular carcinoma (HCC), wherein the HCC cells overexpress a MAGEB2 polypeptide comprising the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) as compared to a panel of normal tissues, wherein the HCC cells present at the cell surface a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) in a complex with HLA-A*02, comprising
 isolating CD8+ cytotoxic T cells, 
 contacting the CD8+ cytotoxic T cells with an antigen presenting cell that present at the cell surface a peptide consisting of SEQ ID NO. 303 in a complex with HLA-A*02 in vitro, thereby activating the CD8+ cytotoxic T cells, and 
 administering to said patient who has HCC a composition comprising a population of the activated antigen-specific CD8+ cytotoxic T cells to kill the HCC cells in the patient, 
 wherein the population of the activated antigen-specific CD8+ cytotoxic T cells recognize the HCC cells by interacting through their TCR with a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) in a complex with HLA-A*02 presented at the surface of the HCC cells. 
 
     
     
       8. The method of  claim 7 , further comprising expanding the activated T cells in vitro. 
     
     
       9. The method of  claim 7 , wherein the composition further comprises an adjuvant. 
     
     
       10. The method of  claim 9 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, OM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23. 
     
     
       11. The method of  claim 7 , wherein the antigen presenting cell in a dendritic cell or a macrophage. 
     
     
       12. The method of  claim 8 , wherein the expanding is in the presence of an anti-CD28 antibody and IL-12.